PROJECT SUMMARY The long-term goal of this research is to address an important health disparity faced by Mexican Americans suffering from Alzheimer's disease (AD) and mild cognitive impairment (MCI), younger age of onset of AD and MCI. AD is the most common form of neurodegenerative dementia and the 5th leading cause of death for those over 65 (8th leading cause of death for U.S. Hispanics). AD has an annual health care cost that is greater than that of cardiovascular disease (CVD) and cancer. While death rates from CVD and cancer have declined in recent decades, death rates have steadily increased for AD. The Mexican American elderly population is among the fastest growing segments of the population; however, little research on MCI and AD has been conducted among this underserved group. Here we will leverage our ongoing Health & Aging Brain among Latino Elders (HABLE; R56AG054073) study to conduct the first-ever test of the amyloid hypothesis within this underserved community. We will determine if amyloid burden is related to younger age of onset experienced by Mexican Americans. We will also study prodromal AD (i.e. normal cognition + amyloid positivity) among community-dwelling Mexican Americans. The current research team consists of leading experts in Mexican American cognitive aging and neuroimaging biomarkers of MCI/AD. The project leverages the ongoing NIH-funded HABLE infrastructure and data (including 3T MRIs) to address the following specific aims: Aim 1: Examine the prevalence and impact of amyloid burden among community-dwelling Mexican Americans suffering from MCI and AD; Aim 2: Examine prodromal Alzheimer's disease among community-dwelling Mexican Americans; and Aim 3. Examine plasma exosome amyloid among community-dwelling Mexican Americans. The current study is highly significant for several reasons: (1) this is the first-ever study of the amyloid hypothesis among Mexican Americans; (2) this study will examine how amyloid contributes to potentially different biological pathways for AD and MCI among Mexican Americans; (3) this study will generate a blood- based tool as the first-step in determining which Mexican Americans should undergo more costly amyloid PET scans for confirmatory diagnosis; and (4) this study will provide a tool for increased enrollment of Mexican Americans into clinical trials (treatment and prevention) directly from primary care settings.